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Biomedical subjects

P R Smith

Publications and source records attributed to P R Smith.

At least 19 recordsLinked to original sources
PubMed1992

Mechanism of the degradation of non-enzymatically glycated proteins under physiological conditions. Studies with the model fructosamine, N epsilon-(1-deoxy-D-fructos-1-yl)hippuryl-lysine.

The degradation of fructosamines, formed from the non-enzymic glycation of proteins under physiological conditions, to advanced glycation end products was investigated by studying the model peptide fructosamine N epsilon-(1-deoxy-D-fructos-1-yl)hippuryl-lysine (DHL). At pH 7.4 and 37 degrees C in aerobic phosphate buffer, DHL degraded to form N epsilon-carboxymethyl-hippuryl-lysine, and hippuryl-lysine over a 29-day incubation period. The expected N epsilon-(3-lactato)hippuryl-lysine and 'hippuryl-lysylpyrraline' derivatives were not found. Superoxide radicals and hydrogen peroxide were formed during the degradation of DHL but were also both consumed during the degradation reaction. Reversal of the Amadori rearrangement was not a major fate of the fructosamine. The formation of N epsilon-carboxymethyl-hippuryl-lysine was decreased by desferrioxamine, catalase, superoxide dismutase, catalase with superoxide dismutase, anaerobic conditions and aminoguanidine. The formation of hippuryl-lysine was decreased by desferrioxamine, catalase and catalase with superoxide dismutase, but was increased by the addition of aminoguanidine. N epsilon-Carboxymethyl-serine and unmodified lysine residues are major peptide-based end products in the degradation of lysyl-fructosamine under physiological conditions. Oxygen, redox-active metal ions, catalase, superoxide dismutase and the pharmacological agent aminoguanidine are expected to be influential on the rate and fate of fructosamine degradation.

Anaerobiosis↗
PubMed1992

Expression of a family of complementary-strand transcripts in Epstein-Barr virus-infected cells.

A major family of polyadenylylated cytoplasmic transcripts are expressed from the BamHI A-I region of the Epstein-Barr virus genome, off the strand complementary to that encoding several functions associated with viral replication and the lytic cycle, including the DNA polymerase (BALF-5). These complementary-strand transcripts (the main one is about 4.8 kilobases long), expressed in all cell types associated with Epstein-Barr virus, are present at high levels in nasopharyngeal carcinoma tumors. Sequence analysis of clones that correspond to spliced transcripts in a cDNA library from such a tumor, C15, generates a profile of the main complementary mRNA. It contains at least three AUG-initiated open reading frames, the largest of which could be translated to give a polypeptide of about 20 kDa. Evidence from several types of experiments suggests that conditions which support the up (or down) regulation of transcriptional expression from one viral DNA strand within the relevant region of the genome produce the opposite effect on transcripts from the other strand. The capacity for interference between complementary Epstein-Barr viral transcripts offers a mechanism for control of gene expression that may be related to maintenance of viral latency.

Base Sequence↗
PubMed1992

Bronchial metastases from ovarian carcinoma. Report of a case and review of the literature.

A patient with ovarian cystadenocarcinoma developed respiratory insufficiency due to bilateral endobronchial metastases, 6.5 years after treatment of the primary tumor. Ovarian cancers frequently metastasize to the pleura and lung parenchyma. Clinically significant bronchial metastases are rare. Only three cases have been reported previously. As in our patient, bronchial metastases tend to occur after a relatively long interval from diagnosis of the primary tumor, and survival may be prolonged after their appearance.

Bronchial Neoplasms↗
PubMed1992

DNA probe for Aeromonas salmonicida.

A DNA fragment that is specific to Aeromonas salmonicida has been isolated from a genomic DNA library by differential hybridization. The specificity of this fragment as a DNA probe for A. salmonicida was shown by hybridization against reference strains and clinical isolates of A. salmonicida, related aeromonads, and species from several other bacterial genera. The sensitivity of detection by a polymerase chain reaction test, based on this fragment, was approximately two A. salmonicida cells.

Aeromonas↗
PubMed1992

Transcription of the Epstein-Barr virus gene EBNA-1 from different promoters in nasopharyngeal carcinoma and B-lymphoblastoid cells.

Transcriptional expression of the Epstein-Barr virus (EBV) genome has been shown to differ markedly between nasopharyngeal carcinoma (NPC) cells and latent B-cell lines, with a more limited pattern of gene expression seen in NPC. EBNA-1 is the only nuclear antigen so far detected in both NPC and Burkitt's lymphoma cells. We found previously that in a human NPC tumor passaged in nude mice, designated C15, the EBNA-1 mRNA contained a novel splice site in the BamHI Q region of EBV which had not previously been described for B-cell lines. This lies within a region of the EBV genome to which EBNA-1 binds. Here, we further characterize the 5' region of EBNA-1 transcripts and identify two splicing patterns in C15 cells; we show that they are derived from a common promoter region in the BamHI F region of the viral genome. We also demonstrate that this region can function to initiate transcription of the chloramphenicol acetyltransferase gene in epithelial cells and that the promoter region is only partially methylated at CpG sites in the tumor. In contrast, a B-lymphoblastoid cell line derived from C15 uses a conventional promoter in BamHI-C/W for expression of EBNA-1.

Antigens, Viral↗
PubMed1992

Drug-induced lupus pleuritis mimicking pleural space infection.

A 78-year-old man presented with acute lupus pleuritis due to procainamide. The pleural fluid was a turbid, yellow exudate with a WBC count of 53,200/cu mm (70 percent polymorphonuclear leucocytes), LDH of 4,296 IU/L, and pH of 7.195. Although these fluid characteristics suggested pleural space infection, they were due to pleural inflammation from drug-induced lupus. LE cells were present in the fluid and results of microbiologic studies were negative. Clinical and roentgenographic improvement followed discontinuation of procainamide.

Acute Disease↗
PubMed1992

Bioactive and immunoreactive FSH and immunoreactive inhibin concentrations in the ovine fetus.

The bioactive (B) and immunoreactive (I) pituitary contents/concentrations of FSH, together with the plasma concentrations of B-FSH, I-FSH and I-inhibin were determined in ovine fetuses at days 55, 75, 90 and 135 of gestation (day 145 = term). The pituitary contents and concentrations of B-FSH and I-FSH increased in both sexes with gestational age. The female fetuses had significantly (P < 0.01) higher pituitary contents/concentrations of B-FSH and I-FSH than the male fetuses at days 75 and 135. The pituitary B/I ratios of FSH were not significantly different with age or sex. The plasma concentrations of B-FSH remained relatively constant from days 75 to 135, with no significant differences between sexes or with age. In contrast, the plasma concentrations of I-FSH reached a peak at day 90 and then declined towards term in both sexes. At all gestational ages except day 55, the female fetuses had significantly (P < 0.05) higher plasma concentrations of I-FSH than the males. In both sexes, the plasma B/I ratios of FSH were lowest at day 90 and had increased again by day 135, with the male fetuses having significantly (P < 0.05) higher B/I ratios compared with the female group at days 75 and 135 but not at day 90. At all gestational ages, the plasma concentrations of I-inhibin declined throughout gestation in the female fetuses, whereas in the males they reached a nadir at day 75 and then increased towards term. The concentrations of I-inhibin were significantly (P < 0.01) higher in the male fetuses compared with the females.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Influence of pH and phosphate ions on the kinetics of enolisation and degradation of fructosamines. Studies with the model fructosamine, N epsilon-1-deoxy-D-fructos-1-yl-hippuryl-lysine.

Investigation of the rate of enolisation and degradation of the model peptide fructosamine N epsilon-1-deoxy-D-fructos-1-yl-hippuryl-lysine and related monosaccharides revealed the fructosamine to be activated towards enolisation but little of the enolic intermediates proceeded to form advanced glycation endproducts. For the oxidative degradation of monosaccharides, enolisation was rate-limiting. Enolisation of the fructosamine was promoted by hydroxide, phosphate and pyrophosphate buffer ions but not directly influenced by the protonation state of the fructosyl amino group. The formation of advanced glycation end-products may be greatly enhanced in the presence of suitable catalysts (trace metal ions) of the degradation of fructosamine-derived enolic intermediates.

Anions↗
PubMed1992

Bronchitis mimicking opportunistic lung infection in patients with human immunodeficiency virus infection/AIDS.

Purulent bronchitis was identified in 19 of 422 patients undergoing fiberoptic bronchoscopy during a 32-month period because of suspicion of an opportunistic lung infection complicating acquired immunodeficiency syndrome or human immunodeficiency virus infection. Five patients had Pneumocystis carinii pneumonia, but other opportunistic lung infections were excluded in the remaining 14 patients. Characteristics of these 14 patients included fever (greater than 38.3 degrees C), cough, and dyspnea in 14 of 14 patients; purulence of expectorated sputum (11/14); and widened alveolar-arterial oxygen gradient (13/14). Rapid (2 +/- 1.4 days) clinical response (defervescence and resolution of pulmonary symptoms) occurred with antibiotic therapy in 10 of 14 patients. In three patients, there was no improvement, and adult respiratory distress syndrome developed. Bacterial isolates from bronchoalveolar lavage included Streptococcus viridans (n = 12), Haemophilus influenzae (n = 7), Staphylococcus aureus (n = 3). Roentgenographic features of bronchiectasis were present in seven patients. Differential cell counts revealed greater than 50% neutrophils in the bronchial washings of all patients with purulent bronchitis. Neutrophil percentages in bronchoalveolar lavage were as follows: patient with purulent bronchitis without P carinii pneumonia (n = 14), 54.53% +/- 29.18%; patients with purulent bronchitis and concomitant P carinii pneumonia (n = 5), 62% +/- 31.9%. In a control group of 17 patients with P carinii pneumonia who did not have purulent bronchitis, the neutrophil percentage was 6.8% +/- 6.17% (p = less than 0.00001, t-test). Purulent bronchitis appears to be a distinct, treatable entity in patients with HIV infection and may accompany bacterial pneumonia, bronchiectasis, and P carinii pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Amiloride-sensitive sodium channel is linked to the cytoskeleton in renal epithelial cells.

Amiloride-sensitive sodium channels are localized to the microvillar domain of apical membranes in sodium-transporting renal epithelial cells. To elucidate the elements that maintain sodium channel distribution at the apical membrane, we searched for specific proteins associating with the channel. Triton X-100 extraction of A6 epithelial cells reveals that sodium channels are associated with detergent-insoluble and assembled cytoskeleton. Indirect immunofluorescence and confocal microscopy show that sodium channels are segregated to the apical microvillar membrane and colocalize with ankyrin, fodrin, and actin. We document by immunoblot analysis that ankyrin and fodrin remain associated with sodium channels after isolation and purification from bovine renal papillae. 125I-labeled ankyrine can be precipitated by anti-sodium-channel antibodies only in the presence of purified bovine sodium-channel complex. Direct binding of 125I-labeled ankyrin shows ankyrin binds to the 150-kDa subunit of the channel. Fluorescence photobleach lateral-diffusion measurements indicate sodium channels are severely restricted in their lateral mobility. We conclude that ankyrin links the amiloride-sensitive sodium channel to the underlying cytoskeleton and this association may sequester sodium channels at apical microvilli and maintain their polarized distribution in renal epithelial cells.

Amiloride↗
PubMed1991

Differential expression of Epstein Barr viral transcripts for two proteins (TP1 and LMP) in lymphocyte and epithelial cells.

Studies presented here show that some functions of the human herpesvirus, EBV, may be transcriptionally differentially expressed in two cell types which carry the same (C15) isolate of this virus. Of the 'latent' viral functions investigated, only one (TP2) of the episomally-specific genes that encode terminal proteins (TP1 and TP2) is found to be expressed in the C15 epithelial cell tumour environment, whereas both are transcribed--as different, but related, messengers--in a B-cell line generated with virus from the C15 tumour. The other gene investigated is that for latent membrane protein (LMP), which is found in the same region of the EBV genome but on the opposite strand. This gene, apparently transcriptionally silent in B-cell (Burkitt's) lymphomas, is expressed in the C15 epithelial tumour, as well as in other nasopharyngeal carcinomas investigated. Promoter usage in the carcinomas and B-cells appears, in some cases at least, to be cell-type specific. Expression may also be governed by methylation since a chromosomally silent region in the carcinoma (that encompassing TP1) is highly methylated on CpG residues, whereas the active region (encoding TP2 and LMP) is virtually free of such methylation. Our data suggest that there may be selective transcriptional regulation of EBV genes in the two types of cells investigated. Thus, it may be unnecessary to invoke different virus genotypes to account for the two distinct malignancies--Burkitt's lymphoma and nasopharyngeal carcinoma--associated with EBV.

Animals↗
PubMed1991

Applications of confocal microscopy to the study of myelin development and neuron structure.

Confocal laser scanning microscopy has been used to study the localization of myelin basic proteins expressed in nonglial cells, and to probe the three-dimensional structure of central auditory neurons in the lateral superior olive. The paper focuses on the techniques used to obtain the results. The key roles of confocal microscopy and computer image processing of the images obtained are emphasized as they relate to the discovery of essential structural information about these specimens.

Animals↗
PubMed1991

Epithelial sodium conductance in rabbit preimplantation trophectodermal cells.

We examined the development of epithelial Na+ conductance in 6- and 7-day post coitus (p.c.) preimplantation rabbit embryos using the whole-cell patch-clamp technique on dissociated rabbit trophectodermal cells and by immunocytochemical localization using a polyclonal antibody directed against subunits of an apical epithelial Na+ channel on the intact blastocyst. In Day 6 and 7 p.c. trophectodermal cells, we observed an outwardly rectified whole-cell Na+ current. The current-voltage characteristics did not differ between the 6- and the 7-day p.c. cells. Replacement of Na+ with the impermeant cation N-methyl-D-glucamine in the pipette or bath reduced outward currents and inward currents, respectively, indicating that the current was Na(+)-dependent. Treatment of 7-day p.c. cells with 100 microM amiloride, benzamil, or ethylisopropyl amiloride (EIPA) blocked the whole-cell currents within 5 min. However, the current of the Day 6 p.c. embryo was not blocked by amiloride. The amiloride block at Day 7 p.c. was only partially reversible after 15 min of continuous perfusion of the bath with an amiloride-free solution. The apparent dissociation constant (Ki) for amiloride, benzamil, and EIPA was 12, 50, and 16 microM, respectively, when measured 5 min after drug addition. Immunolocalization studies of blastocysts with a polyclonal antibody raised against a high amiloride affinity Na+ channel isolated from bovine kidney revealed no specific binding to the trophectodermal cells at Day 6 p.c.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1991

A mechanism for maintaining an up-to-date GenBank database via Usenet.

In this paper, we describe an automated system for distributing updates to the GenBank nucleic acid sequence database, using the Usenet news system as the underlying transport mechanism. Our system allows new loci to be distributed as soon as the sequences are available, over existing networks, using existing Usenet software and infrastructure currently available on a wide range of computer systems.

Amino Acid Sequence↗
PubMed1991

A simple approach for the distribution of computationally intense tasks in an heterogeneous environment: distribution of the MDPP image-processing package.

A method has been developed to link the display ability of a high-resolution graphics workstation with the computational power of a local mainframe or a remote supercomputer via an electronic data network. The method allows this link to be established in a manner largely transparent to the user. The application of the method is illustrated by our successful distribution of the computationally intensive portions of an imaging program (MDPP) from a small VAX workstation to a VAX mainframe and Cray Y-MP8/832 using a simple message-passing technique. This technique can be applied to almost any configuration of networked machines.

Algorithms↗
PubMed1991

Increased metacarpal bone mass following 18 months of slow-acting antirheumatic drugs for rheumatoid arthritis.

Osteoporosis in RA is mediated by numerous inflammatory substances. This study was undertaken to see if SAARD could modify the rate of metacarpal bone loss in RA. Combined cortical thickness (CCT) measured at the midshaft of the right second metacarpal was used to calculate bone mass (CA%) using a digitizer. Eighty-one subjects were studied, all of whom had at least three sets of hand X-rays, the last of which was approximately 18 months following initiation of SAARD therapy. There were 12 males and 69 females. The mean age at time of starting therapy was 51 (SD 12) years while the mean duration of disease at the time was 7.6 (SD 8) years. The mean time to referral for SAARD from the general clinic was 2.5 (SD 3) years. The percentage fall in bone mass prior to therapy was 2.51%/day compared to a gain of 0.6%/day after therapy (P less than 0.05). Forty-nine patients were aged over 50 years while 32 were 50 years or younger at the time of study. Comparison showed that in the pretreatment period, the rate of change in CCT and CA% was not significantly dependent age (P less than 0.1). During that therapy, the rate of change in CCT and CA% significantly different in the two age groups. Patients aged over 50 years continued to lose bone, but at a slower rate (P less than 0.05). Patients aged 50 years or less either stopped losing or gained metacarpal bone mass during the study period (P less than 0.005). The time to referral for SAARD and disease duration (comparable in the two age groups) did not have a significant effect on changes in CA% during therapy. Change in bone mass could be predicted by change in disease activity. We conclude that SAARD have a significant sparing effect on metacarpal osteoporosis in RA. This positive effect is masked by the overwhelming influence of age (and menopause) and could be missed. Metacarpal osteoporosis seems a pathophysiologically more useful measure of radiological change in RA than erosions or joint space narrowing.

Aging↗